title: Exacerbation of invasive Candida albicans infection by commensal bacteria or a glycolipid through IFN-γ produced in part by iNKT cells.
abstract: BACKGROUND
  The commensal yeast Candida albicans is a major cause of invasive fungal infections. Despite treatment with antifungal agents, the mortality rate attributed to these types of infection is high. Although numerous cases have been reported regarding a poor outcome for patients with bacterial and C. albicans coinfection, the mechanisms by which the coinfecting bacteria exacerbate the C. albicans infection remain elusive.
  
  
  RESULTS
  We evaluated how glycolipid-mediated activation of invariant natural killer T (iNKT) cells affects the clearance of C. albicans. Surprisingly, C. albicans-infected, glycolipid-treated mice exhibited significantly lower survival rates, increased fungal burden, and higher interleukin (IL)-6 production in the kidneys compared with control mice. Glycolipid-induced exacerbation of C. albicans infection was not observed in interferon-gamma knockout (IFN-γKO) mice. In the C. albicans-infected, glycolipid-treated mice, the number of neutrophils in the blood and bone marrow dramatically decreased in an IFN-γ-dependent manner. Furthermore, mice that were coinfected with C. albicans and nonfermentative gram-negative commensal bacteria exhibited increased fungal burden and inflammatory cytokine production in the kidneys that were dependent on IFN-γ and iNKT cells.
  
  
  CONCLUSIONS
  Our results indicate that coinfecting commensal bacteria exacerbate C. albicans infection through IFN-γ produced, in part, by iNKT cells.
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo.
authors.forename: Norihito
authors.initials: N
authors.lastname: Tarumoto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kinjo
authors.forename: Naoki
authors.initials: N
authors.lastname: Kitano
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sasai
authors.forename: Keigo
authors.initials: K
authors.lastname: Ueno
authors.forename: Akiko
authors.initials: A
authors.lastname: Okawara
authors.forename: Yuina
authors.initials: Y
authors.lastname: Izawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Shinozaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watarai
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Haruko
authors.initials: H
authors.lastname: Takeyama
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Maesaki
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Shibuya
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology / Q000382:microbiology / Q000821:virology; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D060085:Coinfection / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D006017:Glycolipids / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D009503:Neutropenia / Q000276:immunology / Q000382:microbiology / Q000821:virology
chemical_list: D006017:Glycolipids; D015850:Interleukin-6; D007371:Interferon-gamma
keywords: Candida albicans; commensal bacteria; glycolipid; iNKT cell; nonfermentative gram-negative bacteria